====Motivation and Background: Syphilis is a bacterial infection that may be either congenital or acquired through sexual contact or by exposure to contaminated needles. The disease is of both individual and public health importance and in addition to its direct morbidity, increases risk of HIV infection and can cause lifelong morbidity in children born to infected mothers. This infection is cause by Treponema pallidum, a spirochete, which is a thin coil-shaped bacterium that enters the body through the mucous membranes or breaks in the skin [1]. Treponema pallidum is an endemic in lower-income countries but occurs at a lower rate in middle-income countries. Treponema pallidum, was first described in 1905, but because of the inability to culture the organism and the limitations of direct microscopy, serologic testing is the mainstay of laboratory diagnosis. Acquired syphilis has four stages, including primary, secondary, latent, and tertiary, and can be spread by sexual contact during the first three of these four stages [1]. The primary stage is defined by a chancre at the site of inoculation. The secondary stage is characterized by a polymorphic rash, lymphadenopathy, and other systemic manifestations. A variable asymptomatic latent period follows, which for epidemiologic purposes is divided into early (<1 year) and late (>1 year) stages. The early stages (primary, secondary, and early latent) are potentially infectious. The tertiary stage is the most destructive and is marked by cardiovascular and neurologic sequelae and gummatous involvement of any organ system [2]. Congenital infection may result in protean early or late manifestations. Unlike many other bacteria causing infectious diseases, the organism remains sensitive to penicillin, and this remains the mainstay of therapy.
Fig 1. T. pallidum spirochete, the pathogen of syphilis.
==
References:
[1] Hook, E. W., Syphilis. Lancet2016.
[2] Singh, A. E.; Romanowski, B., Syphilis: Review with emphasis on clinical, epidemiologic, and some biologic features. Clinical Microbiology Reviews1999,12 (2), 187-+.
[3] Hook, E. W.; Marra, C. M., ACQUIRED SYPHILIS IN ADULTS. New England Journal of Medicine1992,326 (16), 1060-1069.
[4] Bicillin® L-A (penicillin G benzathine injectable suspension) Disposable Syringe (accessed Feb 5, 2017)).
[7] Ho EL, Lukehart SA. Syphilis: using modern approaches to understand an old disease. The Journal of Clinical Investigation. 2011;121(12):4584-4592. doi:10.1172/JCI57173.
Target Information:The target of the drug of interest, PGB, is to inhibit the multiplication and biosynthesis of bacterium Treponema pallidum interfering with bacterial cell wall synthesis during active multiplication [4].
Size: molecular weight of the protein: T. Pallidum is very small in size with a length that ranges from 6 to 20 um and a diameter range of 18-20 um. T. pallidum is a member of the spirochete family which are characterized by their distinct helical shape.
Location: T. pallidum are found intracellularly within the cytoplasmic substance of fibroblasts, interstitial and Leydig cells, and of spermatocytes
Function in a normal cell: T. pallidum imports molecules via 18 ATP-binding cassettes which are each specific for certain carbohydrates, amino acids or cofactors.
Drug Information:
Schematic figure of drug:
Fig. 2 Schematic figure of Bicillin L-A
Formula: C48H56N6O8S2
Molecular weight: 909.1364 g/mol
Fig 3. Chemical structure of penicillin G Benzathine (Bicillin L-A)
CAS Number: 1538-09-6
Delivery method: administered by a deep intramuscular injection
Side effects:
skin rashes (including maculopapular eruptions and exfoliative dermatitis Urticaria)
chills
fever
edema
arthralgia
prostration
anaphylaxis (including shock and death)
Other names: Bicillin L-A, Benzylpenicillin, Penicillin G, Penicillin G K for Inj; Bicillin LA; Pfizerpen
Maker or company: Pfizer
Is it patented? yes, it was patented as Benzathine benzylpenicillin in 1950
Clinical Trials Info: So far there are 34 studies found for Penicillin G Benzathine on the ClinicalTrial.Gov Database.
Origin: Benzathine is originated by the reaction of dibenzylethylene diamine with two molecules of Penicillin G. It’s a natural antibacterial antibiotic derived directly from strains of fungi of the genus Penicillium and other soil-inhabiting fungi grown on special culture media.
Alternatives to this drug: The treatment of persons who are allergic to penicillin involves the use of other antibiotics, which may require the administration of multiple doses; therefore, their efficacy depends on the compliance of the patient [3]. Studies of tetracycline (24 to 32 g given over a period of two weeks) have shown that its efficacy is similar to that of penicillin; doxycycline can be considered equally efficacious [3].
Miscellaneous: Persons who receive syphilis treatment must abstain from sexual contact with new partners until the syphilis sores are completely healed. Also, people who had syphilis must notify their sex partners so that they also can be tested and receive treatment if is necessary.
Other uses: can this drug be used to treat other diseases/conditions? Penicillin G Benzathine can also be used to treat mild-to-moderate infections of the upper-respiratory tract due to susceptible streptococci, as well as Venereal infections (yaws, bejel, and pinta) [4]. Rheumatic fever and/or chorea can also be treated as Prophylaxis with penicillin G benzathine, which has proven effective in preventing recurrence of these conditions. It has also been used as follow-up prophylactic therapy for rheumatic heart disease and acute glomerulonephritis [4].
Disease/Drug of interest:
====Motivation and Background: Syphilis is a bacterial infection that may be either congenital or acquired through sexual contact or by exposure to contaminated needles. The disease is of both individual and public health importance and in addition to its direct morbidity, increases risk of HIV infection and can cause lifelong morbidity in children born to infected mothers. This infection is cause by Treponema pallidum, a spirochete, which is a thin coil-shaped bacterium that enters the body through the mucous membranes or breaks in the skin [1]. Treponema pallidum is an endemic in lower-income countries but occurs at a lower rate in middle-income countries. Treponema pallidum, was first described in 1905, but because of the inability to culture the organism and the limitations of direct microscopy, serologic testing is the mainstay of laboratory diagnosis. Acquired syphilis has four stages, including primary, secondary, latent, and tertiary, and can be spread by sexual contact during the first three of these four stages [1]. The primary stage is defined by a chancre at the site of inoculation. The secondary stage is characterized by a polymorphic rash, lymphadenopathy, and other systemic manifestations. A variable asymptomatic latent period follows, which for epidemiologic purposes is divided into early (<1 year) and late (>1 year) stages. The early stages (primary, secondary, and early latent) are potentially infectious. The tertiary stage is the most destructive and is marked by cardiovascular and neurologic sequelae and gummatous involvement of any organ system [2]. Congenital infection may result in protean early or late manifestations. Unlike many other bacteria causing infectious diseases, the organism remains sensitive to penicillin, and this remains the mainstay of therapy.
==
References:
External links:
https://www.cdc.gov/std/tg2015/syphilis.htmhttps://pubchem.ncbi.nlm.nih.gov/compound/25137901
https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=5765
Target Information: The target of the drug of interest, PGB, is to inhibit the multiplication and biosynthesis of bacterium Treponema pallidum interfering with bacterial cell wall synthesis during active multiplication [4].
Size: molecular weight of the protein: T. Pallidum is very small in size with a length that ranges from 6 to 20 um and a diameter range of 18-20 um. T. pallidum is a member of the spirochete family which are characterized by their distinct helical shape.
Location: T. pallidum are found intracellularly within the cytoplasmic substance of fibroblasts, interstitial and Leydig cells, and of spermatocytesFunction in a normal cell: T. pallidum imports molecules via 18 ATP-binding cassettes which are each specific for certain carbohydrates, amino acids or cofactors.
Drug Information:
Schematic figure of drug:
Formula: C48H56N6O8S2
Molecular weight: 909.1364 g/mol
CAS Number: 1538-09-6
Delivery method: administered by a deep intramuscular injection
Side effects:
Other names: Bicillin L-A, Benzylpenicillin, Penicillin G, Penicillin G K for Inj; Bicillin LA; Pfizerpen
Maker or company: Pfizer
Is it patented? yes, it was patented as Benzathine benzylpenicillin in 1950
Clinical Trials Info: So far there are 34 studies found for Penicillin G Benzathine on the ClinicalTrial.Gov Database.
Origin:
Benzathine is originated by the reaction of dibenzylethylene diamine with two molecules of Penicillin G. It’s a natural antibacterial antibiotic derived directly from strains of fungi of the genus Penicillium and other soil-inhabiting fungi grown on special culture media.
Alternatives to this drug:
The treatment of persons who are allergic to penicillin involves the use of other antibiotics, which may require the administration of multiple doses; therefore, their efficacy depends on the compliance of the patient [3]. Studies of tetracycline (24 to 32 g given over a period of two weeks) have shown that its efficacy is similar to that of penicillin; doxycycline can be considered equally efficacious [3].
Miscellaneous: Persons who receive syphilis treatment must abstain from sexual contact with new partners until the syphilis sores are completely healed. Also, people who had syphilis must notify their sex partners so that they also can be tested and receive treatment if is necessary.
Other uses: can this drug be used to treat other diseases/conditions?
Penicillin G Benzathine can also be used to treat mild-to-moderate infections of the upper-respiratory tract due to susceptible streptococci, as well as Venereal infections (yaws, bejel, and pinta) [4]. Rheumatic fever and/or chorea can also be treated as Prophylaxis with penicillin G benzathine, which has proven effective in preventing recurrence of these conditions. It has also been used as follow-up prophylactic therapy for rheumatic heart disease and acute glomerulonephritis [4].